1. Field of the Invention
The present invention relates to bis(2-aryl-5-pyridyl) derivatives or salts thereof, and to medicinal materials which comprise the bis(2-aryl-5-pyridyl) derivatives or salts thereof as active ingredients and are useful for the prevention or treatment of allergic immune diseases.
2. Discussion of the Background
IgE, a class of immunoglobulin (Ig), is an allergen-specific molecule produced by IgE producing cells differentiated from B cells, when triggered by contact of immunocytes with an allergen in the body.
IgE is produced in a target organ exhibiting an allergic response, and binds to a receptor on the surfaces of mast cells, which are principal effector cells, in an allergic reaction or basophils (sensitized state). Allergic chemical mediators such as histamine, leucotrienes, prostaglandins, and PAF, and tissue destructive enzymes such as tryptase are released from the mast cells, which are stimulated as a result of intrusion of the allergen into the body after sensitization and its reaction with specific IgE, to provoke immediate responses of an allergic reaction such as increased vasopermeability, smooth muscle constriction and vasodilation. Cytokines, such as IL-4, which activate other immune system cells, are also secreted from the stimulated mast cells. As a result, eosinophils, basophils or the like infiltrate tissues, and an allergic chemical mediator or tissue destructive protein such as MBP, which are secreted by these inflammatory cells, induce late responses of the allergic reaction and protract and worsen an allergic symptom.
As can be appreciated from what is stated above, abnormality in IgE production is highly relevant to various allergic immune diseases such as asthma, atopic dermatitis, allergic rhinitis, inflammatory bowel disease, contact dermatitis and allergic ophthalmopathy. It is known that inhibition of IgE production makes it possible to prevent and/or treat these diseases (Emerging Therapeutic Targets In Asthma And Allergy: Modulation Of IgE. Emerging Therapeutic Targets, 3, 229-240 (1990); Anti-IgE As Novel Therapy For The Treatment Of Asthma. Curr. Opin. Plum. Med., 5, 76-80 (1999); Treatment Of Allergic Asthma With Monoclonal Anti-IgE Antibody., N. Eng. J. Med., 341, 1966-1973 (1999); Anti-IgE Antibody Therapy For Asthma. N. Eng. J. Med., 341, 2006-2008 (1999).).
From the foregoing, IgE is believed to be a substance which is involved in the manifestation of an allergic disease from the very beginning. With the objective of developing antiallergic agents, some small molecules with IgE antibody production inhibiting activity have been found and have been reported to date (WO 98/04058, WO 98/07702, WO 98/16497, JP 10-324631A, WO 99/19291, WO 99/35140, WO 99/38829, WO 99/42446, JP 11-269192A, WO 00/05198, “Yakuri to Chiryo (Basic Pharmacology & Therapeutic)”, 22(3), 1369 (1994), JP 1-106818A, JP 7-17506B, JP 8-92216A, JP 8-109177A, WO 96/11682, JP 59-167564A). These compounds, however, involve problems such as low solubility in water, and thus they are not fully satisfactory for the stated reason and other reasons.